Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management.

AL amyloidosis is caused by the excessive production of nonfunctional immunoglobulins, leading to the formation of amyloid fibrils that damage vital organs, especially the heart and kidneys. AL amyloidosis presents with non-specific symptoms such as fatigue, weight loss, numbness, pain, and nephrotic syndrome. Consequently, diagnosis is often delayed, and patients typically present with advanced disease at diagnosis. The Pavia renal staging model stratifies patients based on their likelihood of progressing to dialysis. Treatment with daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (i.e., Dara-CyBorD) was effective in inducing renal response in the landmark phase III ANDROMEDA trial and reducing early mortality. However, determining the most appropriate treatment regimen for relapsed or refractory cases remains a challenge due to various patient- and disease-related factors. Encouragingly, t(11:14) may be a positive indicator of therapy responses to the anti-BCL2 therapy venetoclax. Moreover, it is increasingly possible-for the first time-to clear AL amyloid fibrils from peripheral organs by leveraging novel anti-fibril immunotherapeutic approaches, although these medications are still under investigation in clinical trials. Given these advancements, this review provides a comprehensive overview of the current strategies for diagnosing, staging, treating, and monitoring AL amyloidosis, emphasizing renal involvement.

Management of Relapsed Hairy Cell Leukemia: A Systematic Review of Novel Agents and Targeted Therapies.

BACKGROUND: Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL. METHODS: Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: "hairy cell leukemia" or "leukemia, hairy cell" AND "relapse" or "recurrence". We included only prospective clinical trials with outcome data. RESULTS: Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated. CONCLUSION: Novel agents have good efficacy in HCL in patients with multiple relapses.

Association of Abnormal Metatarsal Parabola With Second Metatarsophalangeal Joint Plantar Plate Pathology.

BACKGROUND: Plantar plate pathology is common, yet it is unclear whether, and to what extent, the length of the second metatarsal contributes to this problem. METHODS: We conducted a retrospective case-control (1:2) study to examine radiographic risk factors for plantar plate tears. One hundred patients (age 55.7 ± 12.3 years) with plantar plate injuries and 200 healthy controls (age 56.3 ± 11.3 years) were included. Cases were defined as patients with nonacute, isolated, plantar plate pathology of the second metatarsophalangeal joint confirmed by intraoperative inspection at a single foot and ankle specialty practice from June 1, 2007, to January 31, 2014. Patients presenting for pain outside of the forefoot served as the control group. Controls were matched on age (±2 years), gender, and year of presentation. Weight-bearing foot x-rays were assessed for several predetermined angular relationships by a single rater. Conditional logistic regression was used to identify risk factors for plantar plate injury. RESULTS: A long second metatarsal, defined as a metatarsal protrusion index less than -4 mm, was the only significant risk factor for plantar plate pathology in both the univariate and multivariable analyses (multivariate odds ratio 2.5 [95% confidence interval 1.8 to 3.3], P = .002). CONCLUSION: We found that a long second metatarsal was a risk factor for developing second metatarsophalangeal joint plantar plate tears. This knowledge may aid foot and ankle surgeons when contemplating the need for second metatarsal shortening osteotomies (eg, Weil osteotomy) during plantar plate surgery and when deciding on the amount of shortening for second metatarsal osteotomies. LEVEL OF EVIDENCE: Level III, retrospective comparative study.